Effect of malnutrition on the pharmacokinetics of anti-TB drugs in Ghanaian children
METHODS: Drug concentrations were measured in Ghanaian children during the intensive phase of TB treatment. Weight-for-age (WFA), height-for-age (HFA), weight-for-height (WFH) and body mass index-for-age (BFA) were calculated and children with Z-scores < -2 SD (standard deviations) were considered as having malnutrition. PK differences of anti-TB drugs were compared by nutritional status.
RESULTS: Of 100 participants, 24/48 (50.0%) of those younger than 5 years had wasting, 58/86 (67.4%) were underweight, and 56/99 (56.6%) had stunting; 22/51 (43.1%) children aged ≥5 years had low BFA. Children with stunting were more likely than controls to have lower mean peak concentration (Cmax) and area under the curve (AUC0–8h) of rifampin (RIF) and pyrazinamide (PZA), as well as a higher frequency of Cmax below the normal range. Wasting and underweight were associated with lower mean ethambutol (EMB) Cmax and AUC0–8h.
CONCLUSIONS: The current WHO-recommended dosages were associated with lower plasma exposure of RIF, PZA and EMB in children with stunting, wasting and underweight. Anti-TB drugs dosing models for children may need to include height.
Keywords: dosing regimen; first-line; pediatric TB; treatment
Document Type: Research Article
Affiliations: 1: Department of Epidemiology, University of Florida, Gainesville, FL, USA, Department of Community Health, University of Ghana Medical School, Kumasi, Ghana 2: Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana, Department of Child Health, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana 3: Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA 4: Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana 5: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa 6: Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA 7: Department of Medicine and Therapeutics, University of Ghana Medical School, Accra, Ghana, Fevers Unit, Korle Bu Teaching Hospital, Accra, Ghana 8: Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
Publication date: 01 January 2021
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